Professor Andy Clark PhD

Andy Clark

Institute of Inflammation and Ageing
Professor of Inflammation Biology

Contact details

Address
Institute of Inflammation and Ageing
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Andy Clark is Professor of Inflammation Biology in the Institute of Inflammation and Ageing. He is a molecular biologist with a long-standing interest in how expression of inflammatory mediators is switched off, contributing to the resolution of inflammation. He is also interested in mechanisms of action of endogenous anti-inflammatory lipids, cytokines and steroid hormones. Andy has received major funding from the Wellcome Trust, MRC and Arthritis Research UK. He has published more than 70 articles and book chapters, many of which have been cited several hundred times.

ORCID ID: 0000-0003-4996-8322

Qualifications

  • PhD, Department of Medicine, University of Birmingham (1992)
  • BA (Hons) Natural Sciences (Genetics), University of Cambridge, UK (1987)

Biography

Andy Clark studied Natural Sciences at the University of Cambridge before doing a PhD in transcriptional regulation of insulin genes at the University of Birmingham. He continued his research at the University of Birmingham for two years, funded by a fellowship from Diabetes UK, before moving to the Cancer Research UK labs in Lincoln’s Inn Fields for three years.

He then worked for almost sixteen years at the Kennedy Institute of Rheumatology, Imperial College London, first as a lecturer, then senior lecturer, then reader. In 2012 Andy was appointed as Professor of Inflammation Biology at the University of Birmingham.

Teaching

Postgraduate supervision

  • Andy supervises laboratory-based research projects for the MSc in Immunology and Immunotherapy
  • Andy has supervised thirteen PhD students to award of degree. Most of these students are still in medical or scientific careers, some in industry, others in academia

Andy is interested in supervising doctoral research students in the following areas:

  • Transcriptional and post-transcriptional gene regulation in the inflammatory response
  • The biology of macrophages in the rheumatoid synovium
  • Anti-inflammatory mechanisms of action of glucocorticoids and interleukin 10

If you are interesting in studying any of these subject areas please contact Professor Andy Clark directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research themes

Inflammation, Resolution, Rheumatology, Gene expression.

Research activity

Control of mRNA stability

Inflammatory mediators such as tumour necrosis factor a (TNFa) are potentially harmful. Their expression is tightly regulated and normally occurs in a transient manner, with rapid induction by a pro-inflammatory stimulus followed by a rapid return to baseline. This pattern of gene expression is dependent on dynamic regulation of mRNA stability. We have characterised a phosphorylation-mediated switch that controls the stability of TNFa and many other pro-inflammatory mRNAs. We recently showed that this switch can be targeted to prevent different forms of experimentally-induced inflammatory pathology. Translational implications of these discoveries are being explored.

Feedback nodes

Resolution of inflammation is partly dependent on negative feedback loops, which ensure that responses to pro-inflammatory stimuli are both transient and proportional. For example, pro-inflammatory stimuli activate the MAPK p38 signalling pathway, promoting expression of inflammatory mediators such as TNFa At the same time, the expression of Dual Specificity Phosphatase 1 (DUSP1) is induced. DUSP1 inactivates p38 to terminate the inflammatory response. Negative feedback mechanisms such as this can also be exploited by anti-inflammatory agonists. For example, the expression of DUSP1 is enhanced and extended by anti-inflammatory glucocorticoids, and this results in more rapid and effective inactivation of inflammatory mediator gene expression. We refer to genes that behave like DUSP1 as “Feedback Node Genes”. Their cooperative regulation by both pro- and anti-inflammatory stimuli is poorly understood, but seems to play a major role in limiting inflammation and preventing chronic inflammatory pathology. We are investigating various Feedback Node Genes and trying to understand the basis of their cooperative regulation.

Other activities

  • Member of the Population and Systems Biology Board of the Medical Research Council
  • Member of the Editorial Board of the Journal of Biological Chemistry
  • Member of the Science Committee of the Society for Endocrinology

Publications

Recent publications

Article

Falconer, J, Pucino, V, Clayton, S, Marshall, JL, Raizada, S, Adams, H, Philp, A, Clark, AR, Filer, A, Raza, K, Young, S & Buckley, C 2021, 'Spontaneously resolving joint inflammation is characterised by metabolic agility of fibroblast-like synoviocytes', Frontiers in immunology, vol. 12, 725641. https://doi.org/10.3389/fimmu.2021.725641

Alivernini, S, MacDonald, L, Elmesmari, A, Finlay, S, Tolusso, B, Gigante, MR, Petricca, L, Di Mario, C, Bui, L, Perniola, S, Attar, M, Gessi, M, Fedele, AL, Chilaka, S, Somma, D, Sansom, SN, Filer, A, McSharry, C, Millar, NL, Kirschner, K, Nerviani, A, Lewis, MJ, Pitzalis, C, Clark, AR, Ferraccioli, G, Udalova, I, Buckley, C, Gremese, E, McInnes, IB, Otto, TD & Kurowska-Stolarska, M 2020, 'Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis', Nature Medicine, vol. 26, no. 8, pp. 1295-1306. https://doi.org/10.1038/s41591-020-0939-8

Clark, A 2019, 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease.', Clinical and Translational Immunology. https://doi.org/10.1002/cti2.1084

Clark, AR & Ohlmeyer, M 2019, 'Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration', Pharmacology & Therapeutics, vol. 201, pp. 181-201. https://doi.org/10.1016/j.pharmthera.2019.05.016

Brown, JM, Ross, E, Desanti, G, Saghir, A, Clark, A, Buckley, C, Filer, A, Naylor, A & Claridge, E 2017, 'Detection and characterisation of bone destruction in murine rheumatoid arthritis using statistical shape models', Medical Image Analysis, vol. 40, pp. 30-43. https://doi.org/10.1016/j.media.2017.05.006

O'Neil, J, Ross, E, Ridley, M, Rosner, D, Crowley, T, Smallie, T, Buckley, C & Clark, A 2017, 'Gain-of-function mutation of tristetraprolin impairs negative feedback control of macrophages in vitro, yet has overwhelmingly anti-inflammatory consequences in vivo.', Molecular and Cellular Biology, vol. 37, no. 11, e00536-16. https://doi.org/10.1128/MCB.00536-16

Tang, T, Scambler, TE, Smallie, T, Cunliffe, HE, Ross, EA, Rosner, DR, O’neil, JD & Clark, AR 2017, 'Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E2, dual specificity phosphatase 1 and tristetraprolin', Scientific Reports, vol. 7, no. 1, 4350. https://doi.org/10.1038/s41598-017-04100-1

Crowley, T, O’neil, JD, Adams, H, Thomas, AM, Filer, A, Buckley, CD & Clark, A 2017, 'Priming in response to pro-inflammatory cytokines is a feature of adult synovial but not dermal fibroblasts', Arthritis Research & Therapy, vol. 19, 35. https://doi.org/10.1186/s13075-017-1248-6

Ross, E, Naylor, A, O'Neil, J, Crowley, T, Ridley, M, Crowe, J, Smallie, T, Tang, JT, Turner, J, Norling, LV, Dominguez, S, Perlman, H, Verrills, NM, Kollias, G, Vitek, MP, Filer, A, Buckley, C, Dean, JL & Clark, A 2017, 'Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression', Annals of the Rheumatic Diseases, vol. 76, no. 3, pp. 612-619. https://doi.org/10.1136/annrheumdis-2016-209424

Bulbrook, D, Brazier, H, Mahajan, P, Kliszczak, M, Fedorov, O, Marchese, FP, Aubareda, A, Chalk, R, Picaud, S, Strain-Damerell, C, Filippakopoulos, P, Gileadi, O, Clark, AR, Yue, WW, Burgess-Brown, NA & Dean, JLE 2017, 'Tryptophan-Mediated Interactions between Tristetraprolin and the CNOT9 Subunit Are Required for CCR4-NOT Deadenylase Complex Recruitment', Journal of Molecular Biology. https://doi.org/10.1016/j.jmb.2017.12.018

Rahman, MM, Rumzhum, NN, Hansbro, PM, Morris, JC, Clark, A, Verrills, NM & Ammit, AJ 2016, 'Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells', Cellular Signalling. https://doi.org/10.1016/j.cellsig.2016.01.009

Clark, A & Dean, JLE 2016, 'The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases', Biochemical Society Transactions, vol. 44, no. 5, pp. 1321-1337. https://doi.org/10.1042/BST20160166

Rahman, MM, Rumzhum, NN, Morris, JC, Clark, AR, Verrills, NM & Ammit, AJ 2015, 'Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin', Scientific Reports, vol. 5, 10063. https://doi.org/10.1038/srep10063

Review article

Crowley, T, Buckley, C & Clark, A 2018, 'Stroma: the forgotten cells of innate immune memory', Clinical & Experimental Immunology, vol. 193, no. 1, pp. 24-36. https://doi.org/10.1111/cei.13149

Falconer, J, Young, S, Clark, A & Buckley, C 2018, 'Synovial cell metabolism and chronic inflammation in rheumatoid arthritis', Arthritis and Rheumatology, vol. 70, no. 7, pp. 984-999. https://doi.org/10.1002/art.40504

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